Project Summary/Abstract The theme of the proposed project is to develop a functional template or atlas of the developing brain based on quantitative cerebral blood flow (CBF) measurements using arterial spin labeling (ASL) perfusion magnetic resonance imaging (MRI). Parenchymal perfusion is an important physiologic parameter in the evaluation and management of brain disorders as well as a surrogate index of neural activity. Such information has been sparse in the pediatric population due to the safety concerns and technical difficulties associated with existing methods to measure perfusion that rely on radioisotopes and contrast agents. ASL perfusion MRI is ideally suited for pediatric perfusion imaging, because it is totally noninvasive and provides high image quality due to unique physiologic properties of a child brain. The capability for absolute CBF quantification is another desirable feature of ASL for longitudinal studies to follow neurodevelopmental changes. Through a pilot Human Brain Project funded by NIMH (R21- MH072576, PI: Wang), we have established the feasibility of pediatric perfusion MRI using ASL, and demonstrated the developmental trajectory of CBF in healthy children as well as perfusion aberrations in pre-clinical and clinical pediatric populations. The proposed R01 project represents a continued and systematic effort to address the functional development of a child brain utilizing ASL perfusion MRI. We will first establish the test-retest repeatability and determine the optimal ASL technique along with imaging parameters for constructing the pediatric perfusion template. The accuracy of ASL CBF measurement in children will be validated using global flow rate to the brain determined by phase contrast MRI technique. In the following 4 years, we will develop the normative developmental template of brain perfusion in healthy children aged 7-16 based on ASL perfusion measurements at baseline. In the last aim, we will characterize the quantitative CBF changes in response to a well-characterized cognitive paradigm - working memory tasks - using a concurrent ASL and BOLD (blood-oxygen-level- dependent) fMRI paradigm. Once developed, the pediatric perfusion template will not only shed light on the evolution of brain function with age, but will also provide a valuable resource and reference system for future developmental neuroscience studies as well as clinical studies on childhood brain disorders.